Synthesis of 6-oxy functionalized campest-4-en-3-ones: efficient hydroperoxidation at C-6 of campest-5-en-3-one with molecular oxygen and silica gel

As a reference compound library for the investigation of biosynthesis of br assinosteroids, focused on a pathway from campesterol (1) to campestanol (2 ), 6-oxy functionalized campest-4-en-3-ones as well as campest-5-en-3-one ( 7) and campestane-3,6-dione were prepared from 1. Oxidation of 1 with pyrid inium chlorochromate buffered by calcium carbonate gave 5-en-3-one (7) in 7 6% yield. Treatment of 7 with silica gel under an oxygen atmosphere in ethy l ether at room temperature produced efficient hydroperoxidation at the C-6 position to give 6 alpha-hydroperoxycampest-4-en-3-one and 6 beta-hydroper oxycampest-4-en-3-one in 34% and 49% yields, respectively. These compounds were converted to 6 alpha-hydroxycampest-4-en-3-one and 6 beta-hydroxycampe st-4-en-3-one by reduction with triethyl phosphite. This provided the first example of the practical use of hydroperoxidation at C-6 of a Delta(5(6))- unsaturated 3-oxo-steroid with molecular oxygen and silica gel. On the othe r hand, oxidation of 1 with pyridinium chlorochromate in the absence of cal cium carbonate gave campest-4-ene-3,6-dione in 64% yield. This compound was then converted in a highly stereoselective manner to campestane-3,6-dione with A/B trans ring junction by reduction with titanium (III) chloride in 8 5% yield.